In Japan, cancer is the leading cause of death. Therefore, cancer control is the highest priority issue from the viewpoint of national health. A basic solution for reducing mortality from cancer is to avoid developing cancer, and “prevention of cancer development and early detection of cancer” are regarded as important. However, because a method for determining cancer susceptibility (a predisposition to cancer) has not yet been fully established, diagnosis and treatment are more focused on early detection (secondary prevention) than on the prevention of cancer development (primary prevention) under the present circumstances. In light of the above, if susceptibility to various types of cancer can be determined in each individual in advance, prevention of cancer development, including improving “lifestyles and living environments” etc., can be effectively accomplished, and not only that, current cancer screening will be efficiently and effectively carried out, hopefully increasing the consultation rate.
Also with regard to breast cancer, several methods for determining the degree of progression of the disease and the risk of developing the disease have been proposed. For example, a method for determining breast cancer, characterized by confirming the presence or absence of the endothelial protein C receptor (EPCR) in a biological sample and determining the subject as positive based on the presence of the above substance has been proposed (see for example, Patent Document 1). This method can be used for the detection of a breast cancer cell, which might be overlooked when only cellular and nuclear morphology is observed; for the detection of a breast cancer cell in the lymph nodes for determination of the degree of lymph node dissection in surgery; and for similar assessment and treatment after metastasis. Also, a method for diagnosing breast cancer in subjects aged 40 years or younger or 55 years or older, comprising the step of obtaining a nucleic acid from a subject and determining a nucleotide at a polymorphic site in the nucleic acid (see for example, Patent Document 2) has been proposed. Further, a method for diagnosing breast cancer or a predisposing factor to develop breast cancer in a subject, comprising the step of determining the expression level of a breast cancer-associated gene in a biological sample derived from a patient and assessing the subject as having breast cancer or a risk of developing breast cancer when the expression level in the sample is increased or decreased in comparison with the level of the gene in a normal control (see for example, Patent Document 3) has been proposed.
A DNA copy number polymorphism (CNP) was reported in 2004 as a condition in which DNA duplication or deletion of as many as about 100 kb in size occurs in a specific chromosomal region. In 2008, it was reported that DNA copy number polymorphisms were present in about 20,000 sites in human genome. A DNA copy number polymorphism is a phenomenon in which the number of copies of several thousand base pairs to several million base pairs varies from one individual to another. Normally, human genes are inherited in two copies in total, one copy from the maternal genome and the other copy from the paternal genome. However, it is known that genes are present in only one copy or three or more copies per cell depending on the individual due to DNA copy number polymorphism in the gene region. As a cause of generating constitutional differences among individuals as observed in various degrees of sensitivity to drugs and various levels of manifestation of side effects, “variation in the nucleotide sequence” of human genes has been widely known as represented by Single Nucleotide Polymorphism (SNP). Also, recently, DNA copy number polymorphism has been receiving increasing attention from the aspect of “variation in the number” of genes.
The present inventors have reported a method for determining endometrial cancer susceptibility and colorectal cancer susceptibility using DNA copy number polymorphism as an index (see Patent Document 4). However, DNA copy number polymorphism enabling determination of breast cancer susceptibility has not hitherto been known.